While multiple monoamines modulate cerebellar output, the mechanistic details of dopaminergic signaling in the cerebellum remain poorly understood. We show that dopamine type 1 receptors (Drd1) are expressed in unipolar brush cells (UBCs) of the mouse cerebellar vermis. Drd1 activation increases UBC firing rate and post-synaptic NMDAR -mediated currents. Using anatomical tracing and in situ hybridization, we test three hypotheses about the source of cerebellar dopamine. We exclude midbrain dopaminergic nuclei and tyrosine hydroxylase-positive Purkinje (Pkj) cells as potential sources, supporting the possibility of dopaminergic co-release from locus coeruleus (LC) axons. Using an optical dopamine sensor GRABDA2h, electrical stimulation, and optogenetic activation of LC fibers in the acute slice, we find evidence for monoamine release onto Drd1-expressing UBCs. Altogether, we propose that the LC regulates cerebellar cortex activity by co-releasing dopamine onto UBCs to modulate their response to cerebellar inputs. Pkj cells directly inhibit these Drd1-positive UBCs, forming a dopamine-sensitive recurrent vestibulo-cerebellar circuit.

Our study in CDTI-naïve areas in Nord Kivu and Ituri (Democratic Republic of the Congo, DRC), Lofa County (Liberia) and Nkwanta district (Ghana) showed that a single 8 mg moxidectin dose reduced skin microfilariae density (microfilariae/mg skin, SmfD) better and for longer than a single 150μg/kg ivermectin dose. We now analysed efficacy by study area and pre-treatment SmfD (intensity of infection, IoI).

Four and three IoI categories were defined for across-study and by-study area analyses, respectively. We used a general linear model to analyse SmfD 1, 6, 12 and 18 months post-treatment, a logistic model to determine the odds of undetectable SmfD from month 1 to month 6 (UD1-6), month 12 (UD1-12) and month 18 (UD1-18), and descriptive statistics to quantitate inter-interindividual response differences. Twelve months post-treatment, treatment differences (difference in adjusted geometric mean SmfD after moxidectin and ivermectin in percentage of the adjusted geometric mean SmfD after ivermectin treatment) Clinicaltrials.gov (ID NCT00790998).

Registered on 14 November 2008 in Clinicaltrials.gov (ID NCT00790998).Ralstonia solanacearum causes bacterial wilt disease, leading to severe crop losses. Xylem sap from R. solanacearum-infected tomato is enriched in the disaccharide trehalose. Water-stressed plants also accumulate trehalose, which increases drought tolerance via abscisic acid (ABA) signaling. Because R. solanacearum-infected plants suffer reduced water flow, we hypothesized that bacterial wilt physiologically mimics drought stress, which trehalose could mitigate. We found that R. solanacearum-infected plants differentially expressed drought-associated genes, including those involved in ABA and trehalose metabolism, and had more ABA in xylem sap. Consistent with this, treating tomato roots with ABA reduced both stomatal conductance and stem colonization by R. solanacearum. Treating roots with trehalose increased xylem sap ABA and reduced plant water use by lowering stomatal conductance and temporarily improving water use efficiency. Trehalose treatment also upregulated expression of salicylic acid (SA)-dependenial wilt management.Prescribing error in obstetrics and gynaecology (O&G) poses harm to women and potentially to the foetus and new born. Pharmacists’ interventions have been reported to prevent prescribing error from reaching the patients. Little is reported on the magnitude of prescribing error and pharmacist intervention in a subspecialised outpatient O&G setting. This study aimed to identify the prevalence of prescribing error and pharmacists’ interventions at the O&G outpatient setting. This retrospective study involved screening of prescriptions for commission and omission errors. Acceptance, clinical significance and rationale for pharmacists’ interventions were analysed. Of the 3883 prescriptions screened, 359 (9.2%) prescriptions contained prescribing error, mainly (52.4%) due to commission errors. Among the 395 interventions performed by the pharmacists, 207 (52.4%) were recorded for omission errors. All the interventions were accepted by the prescribers with 65.1% were categorised as ‘very significant’. About 54% of trther research, preferably qualitative in nature, is recommended to explore, identify and address the factors that may hinder clear, accurate and complete prescription writing practices.Antibiotics are used to treat serious illness, but may also be used extraneously or as a preventative measure in many farm animals. This usage increases the potential for unintentional exposure to a variety of organisms. When antibiotics enter aquatic environments, Daphnia magna are especially vulnerable as they filter-feed in freshwater environments. Oxytetracycline (OTC) is a commonly-used broad-spectrum antibiotic used to treat a variety of mammalian diseases. In this study, the impact of OTC on D. magna mortality and gut biota were studied using both cultivation and sequencing-based approaches. Mortality rates were extremely low with the LD50 >2,000ppm. However, OTC impacted abundance and species diversity of intestinal microorganisms in the gut of the D. magna in abundance as well as species diversity. In control organisms, Pseudomonas putida and Aeromonas hydrophila were both present while only P. putida was found in OTC-exposed organisms. Disruption of the intestinal biota in D. magna could have implications on long-term survival, energy expenditure, and reproduction.Tobacco and marijuana are the most common drugs of abuse among pregnant women. Cigarettes have been extensively studied and increase the risk of miscarriage, preterm birth, premature rupture of membranes, placental dysfunction, low birth rate, stillbirth, and infant mortality. There are sparse data on the specific effects of electronic cigarettes and smokeless tobacco in pregnancy. Literature on marijuana in pregnancy is limited by confounding, bias, and the retrospective nature of studies that do not capture contemporary trends in use. However, several studies suggest an association between marijuana and fetal growth restriction, low birth weight, and neurodevelopmental differences in offspring.We outline a call to action for reproductive health researchers to include patient and public involvement (PPI) in research. PPI prioritizes the patient perspective from study design through dissemination of results which centers the people research intends to serve. PPI highlights the patient as an expert in their own condition. PPI that includes groups harmed by health care disparities can draw attention to these harms and generate novel approaches to address them. Numerous frameworks exist for the use of PPI in research. Because obstetrics and gynecology conditions can be particularly sensitive, PPI is crucial in our field.Over the last decades, federal funding for medical research has decreased, while industry funding has increased. The majority of clinical trials are now industry funded. Involvement of industry raises documented concerns of reporting and publication bias, data suppression, and conclusions that may more favorably align with funder motivations rather than study results. However, industry involvement may also lead to scientific innovation, efficiency, and a more rapid timeline to bring new developments to patients. Through a careful review of a manuscript, the reader can understand the nature of industry involvement and interpret the results in this context.The randomized controlled trial has long been recognized as the gold standard of research designs. As small or underpowered trials have become increasingly common in obstetrics and gynecology, it is essential to appraise the trial design and results with a critical eye and understand the limitations of these trials including the potential for selection bias, inability to discriminate uncommon outcomes and the imprecision of point estimates. When small or underpowered trials are designed to be assessed in combination with other trials in high-quality meta-analysis, some of these limitations are minimized.

Post-stroke survivors report that feedback helps to increase training motivation. A wearable system (M-MARK), comprising movement and muscle sensors and providing feedback when performing everyday tasks was developed. The objective reported here was to create an evidence-based set of upper-limb tasks for use with the system.

Data from two focus groups with rehabilitation professionals, ten interviews with stroke survivors and a review of assessment tests were synthesized. In a two-stage process, suggested tasks were screened to exclude non-tasks and complex activities. Remaining tasks were screened for suitability and entered into a categorization matrix.

Of 83 suggestions, eight non-tasks, and 42 complex activities were rejected. Of the remaining 33 tasks, 15 were rejected five required fine motor control; eight were too complex to standardize; one because the role of hemiplegic hand was not defined and one involved water. The review of clinical assessment tests found no additional tasks. Eleven were u stroke rehabilitation. IMPLICATIONS FOR REHABILITATIONRehabilitation technologies that provide feedback on quantity and quality of movements can support independent home-based upper limb rehabilitation.Rehabilitation technology systems require a library of upper limb tasks at different levels for people with stroke and therapists to choose from.A user-defined and evidence-based set of upper limb tasks for use within a wearable sensor device system have been developed.

Despite decades of research, relatively little is known about short-term predictors of suicidal thoughts and behavior. Intensive longitudinal methods are increasingly applied to investigate near-term risk factors of suicidal thoughts in daily life. The aim of this study was to examine short-term predictors of daily-level suicidal thoughts in a high-risk adolescent sample using the interpersonal-psychological theory of suicidal behavior (IPTS) as a guiding framework; the theory proposes that interpersonal experiences of thwarted belongingness in combination with perceived burdensomeness lead to suicidal desire.

Seventy-eight adolescents hospitalized due to suicide risk responded to one survey/day for 28days after discharge (n=1621 unique observations). VH298 inhibitor Multilevel models examined IPTS-informed predictors of same- and next-day suicidal urge intensity.

Partial and time-dependent support for the theory was found. The hypothesized two-way interaction between burdensomeness and thwarted belongingness (either fdolescents. Findings underscore the importance of fostering peer and family relationships in reducing suicidal thoughts in the post-discharge period. Results additionally suggest that both state- and trait-level burdensomeness have lasting influence on suicidal thoughts during this high-risk period. These findings could inform intervention efforts for high-risk youth.Myocardial ischemia, injury and infarction (MI) are the three stages of acute coronary syndrome (ACS). In the past two decades, a great number of studies focused on myocardial ischemia and MI individually, and showed that the occurrence of reentrant arrhythmias is often associated with myocardial ischemia or MI. However, arrhythmogenic mechanisms in the tissue with various degrees of remodeling in the ischemic heart have not been fully understood. In this study, biophysical detailed single-cell models of ischemia 1a, 1b, and MI were developed to mimic the electrophysiological remodeling at different stages of ACS. 2D tissue models with different distributions of ischemia and MI areas were constructed to investigate the mechanisms of the initiation of reentrant waves during the progression of ischemia. Simulation results in 2D tissues showed that the vulnerable windows (VWs) in simultaneous presence of multiple ischemic conditions were associated with the dynamics of wave propagation in the tissues with each single pathological condition.